An area of cytokine research that has received relatively little attention is that of cytokine-induced cellular responses that are not directly related to mitosis. An example of a cytokine capable of inducing these types of cellular activities is TGFb. Earlier, we showed that TGFb induces cellular hypertrophy in cultured vascular smooth muscle cells. Concomitantly, the stimulated cells exhibited an enhanced level of f-actin and an enhanced expression of fibronectin. This observation led to a series of studies on the cellular adhesion molecule, fibronectin, and its interactions with its receptor. With our collaborators, we have identified a new cell adhesion site on fibronectin known as CS1 and its receptor, the integrin a4b1. The minimum essential amino acid sequence for CS1 activities has been shown to be Leu-Asp-VAl. In addition, we found that a weak adhesive activity shown by CS1-E and CS1-C peptides is due to the C-terminal residues, Glu-Ile-Leu. Previously, we had concluded that the amino terminal domain of CS1 enhances the CS1-A activity by stabilizing the conformation of the C-terminal GPEILDVPST sequence; this was based on biological activity data from the Gly-Gly-Gly-Gly and Pro-Gly-Pro-Gly residue insertion peptides. Our high resolution NMR solution conformational analysis of [15N]Leu residues containing CS1 and GP-CS1-A peptides revealed that the peptide conformation is very flexible even though it contains 5 proline residues. Hence, the exact mechanism of CS1-A activity stabilization by the amino terminal domain is still not clear. To resolve this issue we have made two additional peptides and found the following results: an amino acid substitution at Glu18 by Gln led to a small but finite amount of activity loss whereas the substitution at Asp21 by Asn resulted in a significant loss of biological activity for the CS1 peptide analogues.